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Diabetes mellitus is the world’s largest endocrine disorder resulting in multiple aetiologies, involving metabolic disorders of carbohydrate, fat and protein. All forms of diabetes are due to a decrease in the circulating concentration of insulin (insulin deficiency) and a decrease in the response of peripheral tissues to insulin i.e., insulin resistance. According to the World Health Organization projections, the prevalence of diabetes is likely to increase by 35% by the year 2025. In this study, the streptozotocin (STZ)-induced diabetic rats, the activities of membrane-bound adenosine triphosphatases (ATPases) are altered in erythrocytes and in tissues such as liver and kidney. Albino Wistar rats were rendered diabetic by a single intraperitoneal injection of STZ (40 mg/kg body weight). Diabetic rats exhibited significantly (p<0.05) increased levels of plasma glucose and decreased levels of plasma insulin. The activities of total ATPases, (Na++K+)-ATPase, Ca2+-ATPase and Mg2+-ATPase were significantly (p<0.05) decreased in diabetic control rats. Control and diabetic rats were treated with camel milk (250 mL/day) for a period of 45 days. A group of diabetic rats were also treated with glibenclamide (600 μg/kg body weight). After the treatment period, a significant (p<0.05) decrease in the levels of glucose and increase in the levels of plasma insulin and the activities of ATPases in erythrocytes and tissues were observed in diabetic rats treated with camel milk. A similar effect is also observed in the glibenclamide treated rats. But, control rats treated with camel milk did not show any significant (p<0.05) effect in any of the parameters studied. Our study shows that camel milk has the potential to restore the deranged activities of membrane-bound ATPases in STZ-diabetic rats. Further detailed investigation is necessary to find out its mechanism of action.
A possible role of serine/threonine protein phosphatases PP1 and PP2A in the regulation in vitro of the plasma membrane Ca2+-ATPase purified from rat cortical and cerebellar synaptosomal membranes was investigated. Calcium pump, the enzyme responsible for the maintenance of intracellular calcium homeostasis, is regulated by several mechanisms, including phosphorylation by protein kinases. Here we demonstrate that the protein phosphatases action decreased the activity of native Ca2+-ATPase, and increased the stimulatory effect of calmodulin. Moreover, the calcium pump dephosphorylated by PP1 and PP2A revealed the presence of the additional sites, accessible for a PKA-mediated phosphorylation. The subsequent PKA or PKC phosphorylation of the dephosphorylated cortical and cerebellar Ca2+-ATPase differentially regulated its hydrolytic activity. This study confirms that Ca2+-ATPase in nervous cell is phosphorylated in vivo, and shows for the first time that its activity may be directly regulated by PP1 and PP2A.
The amounts of mRNA of subunit-c (proteolipid) of the V-ATPase of mature leaves of Mesembryanthemum crystallinum L. in the state of C3-photosynthesis were analyzed for a time-series of 96 h under constant conditions in continuous light. Fourier-transform analysis of the data showed endogenous oscillations of the mRNA with period lenghts of 48, 24 and 12 h, i.e. harmonic frequency resonances.
The organophosphorus insecticide bromfenvinfos (2-bromo-l-(2,4-dichlorophenyl)vinyl diethyl phosphate) and its methylated homologue methylbromfenvinfos inhibited noncompetitively the activity of (Ca2+ + Mg2+)-ATPase bound to and solubilized from pig erythrocyte membrane. Both enzyme preparations exhibited biphasic substrate curves displaying the existence of two functional active sites with low and high affinity to ATP. Inhibition of activity was more pronounced for bromfenvinfos than for methylbromfenvinfos and the solubilized enzyme preparation was more affected than the bound one. The results of the experiment suggest that the insecticides inhibited the ATPase by binding to a site on the enzyme rather than by interaction with associated lipids, although their presence could weaken the action of the compounds due to the stronger affinity of organophosphorus insecticides for lipids rather than for proteins.
Plasma membrane Ca2+-ATPase (PMCA), encoded by four separate genes, constitutes a high affinity system extruding Ca2+ outside the cell. The nerve growth factor-treated PC12 cell line possesses all four main PMCA isoforms. To evaluate the potential role of PMCA isoforms in the differentiation process, we transiently suppressed the expression of PMCA2 and 3 using the antisense oligonucleotides. In the transfected PC12 cells, we observed morphological changes, slowed neurite extension and diminished survival of the cells. The apparent transport activity and affinity of the calcium pump to Ca2+ were lower in the cells with suppressed PMCA2 and 3 isoforms than in the control cells. Moreover, in the transfected PC12 plasma membranes, the calcium pump was insensitive to stimulation by calmodulin. These findings suggest that PMCA2 and 3 isoforms may be involved in developmental and differentiation processes.
We investigated in the single myocytes of rat heart the effect of blocking of ATP-ase of sarcoplasmic reticulum (SR) on mitochondrial Ca2+ uptake and release. Mitochondrial Ca2+ content was investigated as Mn2+ - resistant fluorescence of Indo 1 - AM loaded into cells. SR ATP-ase was blocked with 10-6 M thapsigargin (Tg). Tg blocked almost completely stimulation Œdependent mitochondrial Ca2+ uptake and slowed down its release despite that the maximal cytosolic Ca2+ concentration was not decreased. We propose that mitochondrial stimulation -dependent Ca2+ uptake is greatly enhanced by [Ca2+ ] built by SR in microdomains adjacent to these organelle.
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